UNIVERSITY OF TENNESSEE HOSPITAL 1924 Alcoa Highway * Knoxville, TN (865) LABEL

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1 1003 UNIVERSITY OF TENNESSEE HOSPITAL 1924 Alcoa Highway * Knoxville, TN (865) LABEL Knoxville Neurology Clinic Orders and Progress tes : NAME: MED REC#: PHYSICIAN: DATE: DATE PHYSICIAN'S ORDERS DATE PROGRESS NOTES EEG Stat Brain death protocol in AM MRI brain with contrast without contrast CT head without contrast w in AM Neuron specific enolase (Labcorp #140624) Somatosensory Evoked Potential (call EEG lab to order) Serum S100 CPK isoenzymes (labcorp test #002154) White Copy - Medical Records Knoxville Neurology Clinic Orders and Progress tes

2 AAN Summary of Evidence-based Guideline for CLINICIANS PREDICTION OF OUTCOME IN COMATOSE SURVIVORS AFTER CARDIOPULMONARY RESUSCITATION This is a summary of the American Academy of Neurology (AAN) -based guideline reviewing all available on the prognostic value of the clinical examination and ancillary investigations (electrophysiologic, biochemical, and radiologic) for poor outcome in comatose survivors after cardiopulmonary resuscitation. is defined as death, unconsciousness after one month, or unconsciousness or severe disability after six months. Please refer to the full guideline for detailed findings and supporting at RECOMMENDATIONS FOR THE PROGNOSTIC VALUE OF THE CLINICAL EXAMINATION Strong (Level A) Weak (Level C) Features of the neurologic examination: Glasgow Coma Scale (GCS) score; Motor part of the GCS; Brainstem reflexes (pupillary light reflexes, corneal reflexes and eye movements) Presence of seizures or myoclonus status epilepticus (defined as spontaneous, repetitive, unrelenting, generalized multifocal myoclonus involving the face, limbs, and axial musculature in comatose patients) Circumstances surrounding CPR: Anoxia time; Duration of CPR; Cause of the cardiac arrest (cardiac vs. noncardiac); Type of cardiac arrhythmia Elevated body temperature The prognosis is invariably poor in comatose patients with absent pupillary or corneal reflexes, or absent or extensor motor responses three days after cardiac arrest (Level A). Patients with myoclonus status epilepticus within the first day after a primary circulatory arrest have a poor prognosis (Level B). Prognosis cannot be based on the circumstances of CPR (Level B). Prognosis cannot be based on elevated body temperature alone (Level C). RECOMMENDATIONS FOR THE PROGNOSTIC VALUE OF ELECTROPHYSIOLOGIC STUDIES Weak (Level C) Somatosensory evoked potential (SSEPs) EEG and evoked/event-related potential (EP) studies The assessment of poor prognosis can be guided by the presence of bilaterally absent cortical SSEPs (N20 response) within one to three days (Level B). Burst suppression or generalized epileptiform discharges on EEG predicted poor outcomes but with insufficient prognostic accuracy (Level C). RECOMMENDATIONS FOR THE PROGNOSTIC VALUE OF BIOCHEMICAL MARKERS Serum neuron-specific enolase (NSE) Serum S100; Creatine kinase brain isoenzyme (CKBB) Intracranial pressure; Brain oxygenation Serum NSE levels >33 µg/l at days one to three post-cpr accurately predict poor outcome (Level B). There are inadequate data to support or refute the prognostic value of other serum and CSF biochemical markers (Level U). There are inadequate data to support or refute the prognostic value of ICP monitoring (Level U). RECOMMENDATIONS FOR THE PROGNOSTIC VALUE OF RADIOLOGIC STUDIES Neuroimaging studies: CT; MRI; PET There are inadequate data to support or refute whether neuroimaging is indicative of poor outcome (Level U).

3 Confounding factors Some factors may confound the reliability of the clinical exam and ancillary tests. Major confounders could include the use or prior use of sedatives or neuromuscular blocking agents, induced hypothermia therapy, presence of organ failure (e.g., acute renal or liver failure) or shock (e.g., cardiogenic shock requiring inotropes). However, studies in comatose patients have not systematically addressed the role of these confounders in neurologic assessment. COMA DECISION ALGORITHM Exclude major confounders Day 3: Absent pupil or corneal reflexes; extensor or absent motor response Day 1-3: SSEP* absent N20 responses** brain stem reflexes at any time (pupil, cornea, oculocephalic, cough) Day 1: Myoclonus status epilepticus Day 1-3: Serum NSE*>33 ug/l** Brain death testing FPR* 0% (0-8.8) FPR 0% (0-3) FPR 0% (0-3) FPR 0.7% (0-3.7) Decision algorithm for use in prognostication of comatose survivors after CPR. The numbers in parentheses are exact 95% confidence intervals. The confounding factors potentially could diminish prognostic accuracy of this algorithm. *NSE = neuron-specific enolase; SSEP = somatosensory evocked potential; FPR = false positive rate. ** These tests may not be available on a timely basis. Serum NSE testing may not be sufficiently standardized. Communication with family and further decision making The complexity of evaluation and various options of decision making require neurologic professional expertise. More than one scheduled meeting with the family is generally required to facilitate a trusting relationship. The neurologist can explain that the prognosis is largely based on clinical examination with some help from laboratory tests. In a conversation with the family, the neurologist may further articulate that the chance of error is very small. When a poor outcome is anticipated, the need for life supportive care (mechanical ventilation, use of vasopressors or inotropic agents to hemodynamically stabilize the patient) must be discussed. Fully informed and more certain, the family or proxy is allowed to rethink resuscitation orders or even to adjust the level of care to comfort measures only. However, these decisions should be made after best interpretation of advance directives or the previously voiced wishes of the patient. This guideline summary is -based. The AAN uses the following definitions for the level of recommendation and classification of. Class I: Prospective, randomized, controlled clinical trial with masked outcome assessment, in a representative population. The following are required: a) primary outcome (s) is/are clearly defined, b) exclusion/inclusion criteria are clearly defined, c) adequate accounting for drop-outs and cross-overs with numbers sufficiently low to have minimal potential for bias, d) relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences OR a statistical, population-based sample of patients studied at a uniform point of time (usually early) during the course of the condition. All patients undergo the intervention of interest. The outcome, if not objective, is determined in an evaluation that is masked to the patients clinical presentations. Class II: Prospective matched group cohort study in a representative population with masked outcome assessment that meets a-d above OR a RCT in a representative population that lacks one criterion a-d OR a statistical, non-referral-clinic-based sample of patients studied at a uniform point in time (usually early) during the course of the condition. Most patients undergo the intervention of interest. The outcome, if not objective, is determined in an evaluation that is masked to the patients clinical presentations. Class III: All other controlled trials including well-defined natural history controls or patients serving as own controls in a representative population, where outcome assessment is independently assessed or independently derived by objective outcome measurement * Objective outcome measurement: an outcome measure that is unlikely to be affected by an observer s (patient, treating physician, investigator) expectation or bias (e.g., blood tests, administrative outcome data) OR a sample of patients studied during the course of the condition. Some patients undergo the intervention of interest. The outcome, if not objective, is determined in an evaluation by someone other than the treating physician. Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion. Recommendation Level: Level refers to the strength of the practice recommendation based on the reviewed literature. Level A=Established as effective, ineffective, or harmful for the given condition in the specified population. (Level A rating requires at least two consistent Class I studies.) Level B=Probably effective, ineffective, or harmful for the given condition in the specified population (Level B rating requires at least one Class I study or at least two consistent Class II studies.) Level C=Possibly effective, ineffective, or harmful for the given condition in the specified population (Level C rating requires at least one Class II study or two consistent Class III studies.) Level U=Data inadequate or conflicting; given current knowledge, treatment is unproven. This is an educational service of the American Academy of Neurology. It is designed to provide members with -based guideline recommendations to assist with decisionmaking in patient care. It is based on an assessment of current scientific and clinical information, and is not intended to exclude any reasonable alternative methodologies. The AAN recognizes that specific patient care decisions are the prerogative of the patient and the physician caring for the patient, based on the circumstances involved. Physicians are encouraged to carefully review the full AAN guidelines so they understand all recommendations associated with care of these patients Montreal Avenue St. Paul, MN (651)

4 AAN Summary of Evidence-based Guideline for PATIENTS AND THEIR FAMILIES PREDICTION OF RECOVERY FROM COMA AFTER CPR This summary will provide you with information about tests that help doctors predict poor recovery from coma after CPR. In this case, poor recovery means death, continued coma after one month, or severe disability after six months. What does it mean to be comatose after successful CPR? When a person has cardiac arrest, the heart stops beating. He or she stops breathing normally and loses pulse and blood pressure. Doctors may use medicine and electric shocks (cardiopulmonary resuscitation, or CPR) to make the heart start beating again. Even when the pulse and blood pressure return after CPR, the brain may already be damaged. In very serious situations, people may remain comatose. These people have their eyes closed; they do not respond to voice or procedures that test for pain. Recovery from coma Recovery from coma after CPR depends on the cause of brain damage, where it occurs, and how serious the damage is. Some people recover basic responses while others regain full awareness. Recovery usually occurs slowly over time. Many people awaken from coma on the same day. In other people, recovery may be delayed. Doctors expect brain damage if the patient does not recover soon after CPR. Patients in a coma for more than one week often have severe brain disability. A persistent vegetative state may develop from a coma after CPR. The eyes may be open and sleep and wake cycles may occur. However, these patients are not aware of their environment. When they remain this way after three months, the vegetative state is almost always permanent. They may recover, but these patients often remain severely disabled and fully dependent on nursing care. Predictors of poor recovery from coma after CPR Doctors use the results of clinical exams and laboratory tests to predict recovery from coma. For some tests, the chance of error is very small. Neurologists from the American Academy of Neurology are doctors who treat diseases of the brain and nervous system. Experts in neurology carefully reviewed all of the available scientific studies about tests that help predict poor recovery from coma after CPR. The research showed that some tests help doctors predict poor recovery after CPR with a high level of certainty. CLINICAL EXAM FINDINGS There is strong * that the following findings from the clinical exam accurately predict poor recovery from coma after CPR: Absent pupillary reflexes or corneal reflexes. The pupil is the black part of the eye. The colored part of the eye is the iris. The iris controls the size of the pupil by shrinking and expanding. The pupil usually gets smaller when light is held in front of it. This is known as the pupillary reflex. The cornea is the clear part of the eye. It covers the iris and pupil. The corneal reflex consists of blinking when the cornea is touched with a small piece of cotton or dripping water solution. Absent or extensor motor responses three days after cardiac arrest. An absent motor response means that there is no movement to pain. An extensor motor response is a reflex movement showing straightening of the arms and legs. This movement happens on its own or in response to pain. There is good * that myoclonus status epilepticus within the first day after CPR accurately predicts poor recovery from coma. Myoclonus status epilepticus is a constant twitching of muscles, including the face or eyelids. It may get worse by touching. Myoclonus status epilepticus is due to very severe damage to the brain. It is difficult to treat. There is good * that the following clinical findings do not accurately predict poor recovery from coma: The circumstances surrounding CPR. These include anoxia time, duration of CPR, and the type of the cardiac arrest. Anoxia time is the amount of time that passes between cardiac arrest and starting CPR. Hyperthermia. This is an increase in body temperature (a fever).

5 ELECTROPHYSIOLOGIC TESTS Electrophysiologic tests include somatosensory evoked potential (SSEP), electroencephalogram (EEG), and evoked/event-related potential (EP) studies. An SSEP measures the electrical signals of sensation that travel from the body to the brain. The signals are in response to mild electrical stimulation repeated in different parts of the body. The signals are measured on the left and right sides of the body. The electrical activity is shown as a wave. There are different kinds of peaks in the wave. One peak is called an N20 component of the SSEP. There are left and right parts of the N20 component. The N20 component represents the cortex. This is the outer layer of the brain that controls feeling, planned muscle movement, thought, reasoning, and memory. There is good * that an absent N20 component of the SSEP (left and right) within one to three days after CPR accurately predicts poor recovery from coma. An EEG is a test that records electrical activity produced by the brain. The electrical activity of the brain may slow down after a major brain injury. There is not enough * that the results of an abnormal EEG test accurately predict poor recovery from coma after CPR. BIOCHEMICAL TESTS Biochemical tests include proteins such as serum neuron-specific enolase (NSE), S100, and creatine kinase brain isoenzyme (CKBB). Other tests may measure brain oxygenation and intracranial pressure. Serum NSE is a protein found in the blood after there is damage to the brain cells. There is good * that serum NSE levels greater than 33 micrograms per liter measured one to three days after CPR accurately predict poor recovery. There is not enough * that abnormal findings in the following tests accurately predict poor recovery for a comatose patient after CPR: Proteins, such as S100 and creatine kinase brain isoenzyme (CKBB). These are proteins found in brain tissue. Monitoring of brain oxygenation. These are tests that measure the levels of oxygen in the brain. Monitoring of intracranial pressure. These are tests that measure the pressure of brain tissue. BRAIN IMAGING STUDIES Doctors use different methods to take pictures of brain structure and function. Some common imaging techniques include computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). There is not enough * that abnormal brain imaging tests accurately predict poor recovery for a comatose patient after CPR. LIFE-SUPPORTIVE CARE AND ADVANCE DIRECTIVES When poor recovery is expected, family members or caretakers should discuss the need for life support. Fully informed, they can rethink medical orders and adjust the level of care. These decisions should be made after understanding advance directives. Advance directives can be stated out loud and/or written earlier by the patient. They tell the doctor what kind of care the patient would like to receive in case he or she cannot actively participate in making medical decisions. For example, a patient in a permanent coma would not be able to make a medical decision. Talk to your neurologist Family members and caretakers of a person in a state of coma should talk with a neurologist. Neurologists can provide correct information about assessment and recovery. They can also discuss levels of care and life support options. Ask your neurologist for more information and available services. * After the experts review all of the published research studies they describe the strength of the supporting each recommendation: Strong = More than one high-quality scientific study Good = At least one high-quality scientific study or two or more studies of a lesser quality Weak = The studies, while supportive, are weak in design or strength of the findings t enough = Either different studies have come to conflicting results or there are no studies of reasonable quality This is an -based educational service of the American Academy of Neurology. It is designed to provide members and patients with -based guideline recommendations to assist with decision-making in patient care. It is based on an assessment of current scientific and clinical information, and is not intended to exclude any reasonable alternative methodologies. The AAN recognizes that specific patient care decisions are the prerogative of the patient and the physician caring for the patient, based on the circumstances involved Montreal Avenue St. Paul, MN (651)